Immobilizing objects in the body

ABSTRACT

Stabilizing an object in the body of a patient involves the injection of a lower critical solution temperature (LCST) material or other flowable material into the body of the patient so that the material contacts the object. The LCST material or other flowable material then forms a gel in the body such that the object is contained at least partially within the gel and thereby stabilized by the gel such that the object can then be easily fragmented within the body and/or retrieved from the body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part of U.S. patent application Ser. No.09/795,635, filed on Feb. 28, 2001, the entire disclosure of which isincorporated by reference herein.

TECHNICAL FIELD

This invention generally relates to medical instruments and methods forretrieving material from within a body. More particularly, the inventionrelates to retrieval methods, devices, and compositions for stabilizingand removing stones such as urinary tract stones, gall stones, and otherobjects found in the body.

BACKGROUND INFORMATION

Medical retrieval devices generally are used to retrieve biological andforeign material, such as kidney stones and other calculi, from the bodyof a patient. Such medical retrieval devices may be used with anendoscope or a laparoscope. The use of such devices to capture foreignmaterial like stones is made difficult by the freedom of movement of thestones within the body. A stone may dislodge from its resting place whencontacted by a retrieval device. This may cause the stone to move intoan area of the body that renders the stone inaccessible or undetectable,thus preventing the capture and removal of the stone.

Larger stones often need to be shattered because their size prohibitsnon-surgical removal from the body. Shattering a stone (by, for example,light, chemical, or physical energy) can disperse the resulting stonefragments from the original location of the stone. Stone fragments thatare not removed from the body can form the nuclei for the formation ofnew stones. The dispersal of the fragments caused by the shatteringprocess can cause fragments to move into inaccessible or unknown areasof the body, thus preventing or interfering with the capture and removalof the fragments.

SUMMARY OF THE INVENTION

It is an object of the invention to facilitate the capture and removalof objects located within the body. The invention generally includes theuse of a material or materials that exist in liquid form and istransformed into a gel inside the body of a patient. In one aspect, theinvention generally includes the use of a material that exists in liquidform at temperatures below about body temperature and as a gel attemperatures about at and above body temperature. The temperature atwhich the transition from liquid to gel occurs is referred to as thelower critical solution temperature (LCST), and it can be a smalltemperature range as opposed to a specific temperature. Materialsappropriate for use according to the invention possess a LCST and arereferred to as LCST materials.

The methods and systems of the present invention generally involve theinjection of an LCST material into a cavity or space within the body.Once inside the body, the LCST material can contact and at leastpartially contain an object. In many cases, the LCST will entirelyenvelop and surround the object. As the temperature of the LCST materialrises due to the internal temperature of the body, the LCST materialwill reach its LCST and thus transition into the gel phase. The specifictransition point or range is determined by the specific LCST materialutilized. An object in contact with the LCST material can be at leastpartially trapped and stabilized by the gel. The stabilization of theobject allows for easier capture and retrieval of the object.Stabilization of the object also allows for easier use of a lithotripsydevice for fragmenting the object because the gel holds the object inplace. Furthermore, the gel prevents the free dispersal of fragments ofthe object after the object is broken apart by the lithotripsy device.Preventing the dispersal of the fragments allows for easier capture andretrieval of the object fragments.

The invention also relates to materials other than LCST materials thatare in a flowable form outside of the patient's body and may betransformed into a gel form inside the patient's body. A materialincluding crosslinkable polymers may be in a flowable form and uponcontact with a crosslinking agent be transformed into gel form. The gelformed from a material including crosslinkable polymers functionssimilarly to the LCST material by contacting and stabilizing an objectin the patient's body. The gel formed from the crosslinkable polymersmay be dissolved by contact with a de-crosslinking agent. Ade-crosslinking agent weakens or removes the bonds within the network ofcrosslinkable polymers that forms the gel. Once the gel is dissolved thematerial returns to a flowable form and may be more easily removed fromthe patient's body.

Other materials related to the invention include gelatin materials.Gelatin materials exist in liquid form at temperatures above about bodytemperature and as a gel at temperatures below about body temperature.The gelatin material is cooled after it is injected into the patient'sbody in order to transform the gelatin material into a gel form. Coolingof the gelatin material can be performed by contacting the gelatinmaterial with a liquid that is at a temperature below about bodytemperature. Water or a buffer at a temperature below about bodytemperature may be injected concurrently with the injection of thegelatin material, for example.

The invention, in one aspect, includes a method of stabilizing an objectin the body of a patient. The method includes injecting a lower criticalsolution temperature material in a flowable form into the body of thepatient to contact the object. The method further includes allowing thelower critical solution temperature material to form a gel in the bodydue to a temperature inside the body. The object thus is contained atleast partially within the gel and stabilized by the gel.

In one embodiment according to this aspect of the invention, the methodinvolves the use of the lower critical solution temperature (LCST)material that remains in the flowable form below about the temperatureinside the body of the patient. The LCST material can form the gel aboutat and above the temperature inside the body of the patient.

In other embodiments, the method can include retrieving the stabilizedobject from the gel and/or breaking the object into at least twofragments. At least some of the fragments remain at least partiallywithin the gel and stabilized by the gel, and these fragments can thenbe retrieved from the gel.

In another aspect, the invention relates to a system for stabilizing anobject in the body of a patient. The system includes a lower criticalsolution temperature material which remains in a flowable form belowabout a temperature inside the body of the patient and which forms a gelabout at and above the temperature inside the body of the patient. Thesystem also includes a catheter for transferring the lower criticalsolution temperature material into the body in the flowable form and aguide wire for introducing the catheter into the body and guiding it toabout the location of the object. The system also includes a mechanismto force the lower critical solution temperature material in theflowable form through the catheter and into the body to contact theobject. The lower critical solution temperature material gels inside thebody due to the temperature inside the body and thereby contains atleast a portion of the object within the gel to stabilize the object.One embodiment according to this aspect of the invention involves theuse of the catheter to remove the lower critical solution temperaturematerial from the body.

In still another aspect, the invention features a system for stabilizingan object in the body of a patient. The system includes a lower criticalsolution temperature material which remains in a flowable form belowabout a temperature inside the body of the patient and which forms a gelabout at and above the temperature inside the body of the patient. Thesystem also includes a percutaneous access device for transferring thelower critical solution temperature material into the body in theflowable form. The system further includes a mechanism to force thelower critical solution temperature material in the flowable formthrough the percutaneous access device and into the body to contact theobject. As before the lower critical solution temperature material gelsonce inside the body due to the temperature inside the body and therebycontains at least a portion of the object within the gel to stabilizethe object.

In one embodiment according this aspect of the invention, thepercutaneous access device comprises a needle. In some embodiments, thesystem further includes a catheter for removing the lower criticalsolution temperature material from the body. In some embodiments of thisand the prior aspects of the invention, the mechanism used to force thelower critical solution temperature material into the body comprises asyringe.

The lower critical solution temperature material used in connection withall aspects of the invention can comprise a block copolymer with reversethermal gelation properties. The block copolymer can further comprise apolyoxyethylene-polyoxypropylene block copolymer such as abiodegradable, biocompatible copolymer of polyethylene oxide andpolypropylene oxide. Also, the lower critical solution temperaturematerial can include a therapeutic agent such as an anti-angiogenicagent.

In another aspect, the invention relates to a method for stabilizing anobject in a patient's body. The method includes injecting a firstmaterial, which includes a crosslinkable polymer in a flowable form,into the patient's body to contact an object. The method also includescontacting the first material with a second material. The secondmaterial includes a crosslinking agent, and the first material andsecond material, upon contact, form a gel in the patient's body. Themethod also includes stabilizing the object in the patient's body byenabling the gel to contact the object.

In an embodiment of the method, the first material includes one or moreof an anionic crosslinkable polymer, a cationic crosslinkable polymer,or a non-ionically crosslinkable polymer. In other embodiments of themethod, the first material includes one or more of polyacrylic acids,polymethacrylic acid, alginic acid, pectinic acids, sodium alginate,potasium alginate, carboxy methyl cellulose, hyaluronic acid, heparin,carboxymethyl starch, carboxymethyl dextran, heparin sulfate,chondroitin sulfate, polyethylene amine, polysaccharides, chitosan,carboxymethyl chitosan, cationic starch or salts thereof.

In another embodiment of the method, the second material includes one ormore of an anionic crosslinking ion, a cationic crosslinking ion, or anon-ionic crosslinking agent. In other embodiments of the method, thesecond material includes one or more of phosphate, citrate, borate,succinate, maleate, adipate, oxalate, calcium, magnesium, barium,strontium, boron, beryllium, aluminium, iron, copper, cobalt, lead, orsilver ions. In still other embodiments of the method, the secondmaterial includes one or more of di-vinylsulfone, polycarboxylic acids,polycarboxylic anhydrides, polyamines, epihalohydrins, diepoxides,dialdehydes, diols, carboxylic acid halides, ketenes, polyfunctionalaziridines, polyfunctional carbodiimides, polyisocyanate,glutaraldehyde, or polyfunctional crosslinkers including functionalgroups capable of reacting with organic acid groups.

In another embodiment, the method further includes the step ofretrieving the object from the gel. In yet another embodiment, themethod further includes the step of applying energy to the objectcausing it to break into at least two fragments. At least some of thefragments remain at least partially in contact with the gel andstabilized by the gel. In others embodiments of the method, the energyapplied to the object is selected from the group consisting ofmechanical, vibrational, light, chemical, and electromagnetic energy. Inother embodiments of the method, the technique for breaking the objectinto at least two fragments is selected from the group consisting ofextra-corporeal shock wave lithotripsy, intra-corporeal shock wavelithotripsy, or Holmium laser fragmentation.

In another embodiment, the method further includes the step ofretrieving at least some of the fragments from the gel. In oneembodiment, the step of retrieving some of the fragments from the gelincludes using a retrieval device to retrieve such fragments.

In yet another embodiment, the method further includes contacting thegel with a third material that includes a de-crosslinking agent. In someembodiments, the third material includes one or more of sodiumphosphate, sodium citrate, inorganic sulfates, ethylene diaminetetraacetic acid and ethylene dime tetraacetate, citrates, organicphosphates (e.g., cellulose phosphate), inorganic phosphates (e.g.,pentasodium tripolyphosphate, mono- and di-basic potassium phosphate,sodium pyrophosphate), phosphoric acid, trisodium carboxymethyloxysuccinate, nitrilotriacetic acid, maleic acid, oxalate, polyacrylicacid, sodium, potassium, calcium, or magnesium ions.

In another aspect, the invention relates a method of fragmenting anobject in a patient's body. The method includes injecting a material ina flowable form into the patient's body to contact an object, allowingthe material to form a gel in the patient's body, and stabilizing theobject in the patient's body by enabling the gel to contact the object.The method also includes applying energy from outside of the patient'sbody that is directed towards the object. The energy directed towardsthe object breaks the object into at least two fragments. In oneembodiment the energy is produced by extra-corporeal shock wavelithotripsy.

In one embodiment according to this aspect of the invention, thematerial includes one or more of a crosslinkable polymer, a gelatinmaterial or a lower critical solution temperature material. In anotherembodiment, the material includes a polyoxyethylene-polyoxypropyleneblock copolymer.

In another embodiment, the method further includes retrieving thestabilized object from the gel. In yet another embodiment, the methodfurther includes breaking the object into at least two fragments. Atleast some of the fragments remain in contact with the gel. In anotherembodiment, the method further includes retrieving the at least some ofthe fragments from the gel. In one embodiment, the method furtherincludes contacting the lower critical solution temperature materialwith a degradation modulating material. In another embodiment, thedegradation modulating material is selected from the group consisting ofpluronic acid, polylactic acid, polyglycolic acid, and hyaluronic acid.

In another aspect, the invention relates to a system for stabilizing anobject in a patient's body. The system includes a first material thatincludes a crosslinkable polymer in flowable form, and a second materialthat includes a crosslinking agent. The first material and secondmaterial, upon contact, form a gel in the patient's body. The systemalso includes a catheter for transferring the first material and secondmaterial into the patient's body in flowable form, such that the gelformed by the first material and second material contacts and therebystabilizes the object. The system also includes a guide wire forintroducing and guiding the catheter into the patient's body.

In yet another aspect, the invention relates to a system for stabilizingan object in a patient's body. The system includes a first material thatincludes a crosslinkable polymer in flowable form, and a second materialthat includes a crosslinking agent. The first material and secondmaterial, upon contact, form a gel in the patient's body. The systemalso includes a percutaneous access device for injecting the firstmaterial and second material into the patient's body in flowable form,such that the gel formed by the first material and second materialcontacts and thereby stabilizes the object.

In embodiments according to the aspects of the invention relating to asystem, the first material includes one or more of an anioniccrosslinkable polymer, a cationic crosslinkable polymer, or anon-ionically crosslinkable polymer. In other embodiments according tothe aspects of the invention relating to a system to the first materialincludes one or more of polyacrylic acids, polymethacrylic acid, alginicacid, pectinic acids, sodium alginate, potasium alginate, carboxy methylcellulose, hyaluronic acid, heparin, carboxymethyl starch, carboxymethyldextran, heparin sulfate, chondroitin sulfate, polyethylene amine,polysaccharides, chitosan, carboxymethyl chitosan, cationic starch orsalts thereof.

In yet other embodiments according to the aspects of the inventionrelating to a system, the second material includes one or more of ananionic crosslinking ion, a cationic crosslinking ion, or a non-ioniccrosslinking agent. In other embodiments according to the aspects of theinvention relating to a system, the second material includes one or moreof phosphate, citrate, borate, succinate, maleate, adipate, oxalate,calcium, magnesium, barium, strontium, boron, beryllium, aluminium,iron, copper, cobalt, lead, or silver ions. In still other embodimentsof the method, the second material includes one or more ofdi-vinylsulfone, polycarboxylic acids, polycarboxylic anhydrides,polyamines, epihalohydrins, diepoxides, dialdehydes, diols, carboxylicacid halides, ketenes, polyfunctional aziridines, polyfunctionalcarbodiimides, polyisocyanate, glutaraldehyde, or polyfunctionalcrosslinkers including functional groups capable of reacting withorganic acid groups.

The foregoing and other objects, aspects, features, and advantages ofthe invention will become more apparent from the following descriptionand from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, like reference characters generally refer to the sameparts throughout the different views. Also the drawings are notnecessarily to scale, emphasis instead generally being placed uponillustrating the principles of the invention.

FIG. 1a illustrates the insertion of a distal end of a guide wire into akidney containing a kidney stone.

FIG. 1b illustrates the insertion of a catheter into the kidney bypassage over the guide wire of FIG. 1a.

FIG. 1c illustrates the removal of the guide wire from the lumen of thecatheter of FIG. 1b and the injection of an LCST material into thekidney through the catheter.

FIG. 1d is similar to FIG. 1c except that FIG. 1d shows the kidney stoneafter being fragmented by, for example, a medical lithotripsy device.

FIG. 1e illustrates the capture of a kidney stone fragment by a medicalretrieval device such as a basket.

FIG. 1f shows the kidney after removal of the kidney stone fragments ofFIGS. 1d and 1 e, and after some of the LCST material has drained and/orbeen removed from the body.

FIG. 2a illustrates the percutaneous insertion of a needle into a kidneycontaining a kidney stone, with a syringe containing an LCST materialconnected to the needle on the outside of the patient's body.

FIG. 2b illustrates the injection of the LCST material from the syringe,through the needle, and into the kidney.

FIG. 2c shows the kidney stone after being fragmented by, for example, amedical lithotripsy device.

FIG. 2d illustrates the capture of a kidney stone fragment by a medicalretrieval device such as a basket.

FIG. 2e shows the kidney after removal of the kidney stone fragments andafter some of the LCST material has drained and/or been removed from thebody.

DESCRIPTION

The invention generally relates to systems and methods for stabilizingobjects (such as kidney stones, gall stones, and other natural andforeign substances) found in the body of a patient (such as a human orother mammal) by the injection of a flowable material into the patient'sbody and the transformation of the material into a gel. The gel contactsand thereby stabilizes the object in the patient's body. The inventioninvolves using materials that become a gel at or above about bodytemperature, materials that become a gel when contacted with acrosslinking agent, and gelatin materials that form a gel attemperatures below about body temperature.

The materials that are the subject of the invention, such as the LCSTmaterials that become a gel at or about body temperature, can beinjected into the patient's body in a liquid form. The injected materialonce reaching body temperature undergoes a transition from a liquid to agel. Objects that are contacted by the material become trapped entirelyor partially within the gel and thus stabilized in place in the body.Medical devices for breaking the object into fragments and/or retrieving(or otherwise eliminating) the object and any of its fragments from thebody can accomplish the breaking and/or removal more easily because thegel causes the object to be fixed in place and does not allow the objectto move freely about the cavity in which it is located in the body.Additionally, fragments of the object that result from breaking theobject with a suitable medical device (such as a laser lithotriptor)generally remain trapped at least partially within the gel, in that thegel also traps the fragments and prevents the scattering of fragmentswithin the body. Kidney stone fragments that remain in the body can formthe nuclei for the growth of other kidney stones.

LCST materials possess a lower critical solution temperature, which isthe temperature at which LCST materials transition from liquid to gelform. Suitable LCST materials include polyoxyethylene-polyoxypropylene(PEO-PPO) block copolymers. Two acceptable compounds are Pluronic acidF127 and F108, which are PEO-PPO block copolymers with molecular weightsof 12,600 and 14,600, respectively. Each of these compounds is availablefrom BASF of Mount Olive, N.J. Pluronic acid F108 at 20-28%concentration in phosphate buffered saline (PBS) is an example of asuitable LCST material. A more preferable preparation is 22.5% Pluronicacid F108 in PBS. A preparation of 22% Pluronic acid F108 in PBS has anLCST of 37° C. Pluronic acid F127 at 20-35% concentration in PBS isanother example of a suitable LCST material. A preparation of 20%Pluronic acid F127 in PBS has an LCST of 37° C. Low concentrations ofdye (such as crystal violet), hormones, therapeutic agents, fillers, andantibiotics can be added to the LCST material. For example, acancer-treating agent such as endostatin can be carried by the LCSTmaterial and thus delivered inside the body via the LCST material. Ingeneral, other PEO-PPO block copolymers that are LCST materials and thatare biocompatible, biodegradable, and exist as a gel at body temperatureand a liquid at below body temperature can also be used according to thepresent invention. The molecular weight of a suitable material (such asa block copolymer) can be, for example, between 5,000 and 25,000, andmore particularly between 7,000 and 15,000, and, for the two specificcompounds identified above, 12,600 or 14,600.

Materials that include crosslinkable polymers and that become a gel whencontacted with a crosslinking agent may be used in accordance with theinvention. An embodiment of the invention relates to injecting amaterial including one or more crosslinkable polymers into the patient'sbody, contacting the crosslinkable polymers with a material includingone or more crosslinking agents and enabling the gel to contact anobject in the body. The material including crosslinkable polymer(s) maycontact the material including crosslinking agent(s) before or afterinjection into the body. If the crosslinkable polymer(s) contact thecrosslinking agent(s) before injection into the body, then mixture ofcrosslinkable polymer(s) and crosslinking agent(s) should be injectedinto the body prior to the crosslinking reaction occurring and thetransformation of the materials into gel form. Contacting the gel formedwith crosslinkable polymer(s) with a de-crosslinking agent dissolves thegel and facilitates its removal. Once the gel is dissolved, it flowsdown the ureter and into the bladder to be expelled from the body withthe urine. The gel may also be removed by extraction of the materialthrough a catheter or a percutaneous access device such as a needle.

Referring to FIG. 1a, distal end of a guide wire 108 is inserted intothe urinary tract until reaching the kidney 100. The guide wire 108 caninclude a controllable tip for the purpose of directing the guide wire108 along the urinary tract. The guide wire 108 could similarly beinserted into other tracts or passageways of the body. A stone 106 ispresent in the calyx 102 of the kidney 100. The stone 106 could also belocated in other locations of the kidney 100 such as the renal pelvis orother locations in the urinary tract such as the ureter 104.

In FIG. 1b, the guide wire 108 serves as a guide for the insertion ofthe distal end of the catheter 110 into the kidney 100. The catheter 110slides over the guide wire 108 with the guide wire 108 located in thelumen of the catheter 110. The catheter 110 may extend into the kidneyso that the distal end of the catheter 110 is disposed near the kidneycalyx 102 and the stone 106.

The guide wire 108 is then withdrawn from the lumen of the catheter 110and is removed from the body, thus leaving the catheter 110 within thebody. The lumen of the catheter 110, unobstructed by the guidewire 108,may transport material in flowable form from the outside of thepatient's body into the patient's body and the calyx 102, for example.The LCST material 112, as an example of a material in a flowable form,starts external to the body and at a temperature below body temperatureand thus in a liquid and flowable form. In some embodiments, the LCSTmaterial 112 could be cooled to a temperature below ambient airtemperature prior to injection to delay the time required for theinjected LCST material 112 to reach body temperature and form a gel, butsuch cooling generally is not required. A mechanism, such as anautomated or human-operated syringe, can be used to force the LCSTmaterial 112 through the catheter 110 and into the kidney 100, as shownin FIG. 1c. The mechanism can be any suitable device that appliespressure to the LCST material 112 to force it in a liquid form throughthe catheter 110 and into the body to contact the object to bestabilized. The LCST material 112 then enters, as a liquid, areas of thekidney 100 including the calyx 102 and the renal pelvis. The LCSTmaterial 112 also generally flows into the ureter 104 and towards theurinary bladder, as depicted in FIG. 1c. As the temperature of the LCSTmaterial 112 inside the body rises toward body temperature, the LCSTmaterial 112 reaches its LCST and transitions into the gel phase. Anobject, like the stone 106, in contact with the LCST material 112 willbe at least partially enveloped by the gel and thus stabilized by thegel. The stabilization of the stone 106 allows for easier capture andretrieval of the stone 106 because the stone 106 is held in place by thegel 112. Additionally, the transition from liquid to gel can cause theLCST material 112 to form a seal or plug in the ureter 104 near therenal pelvis that allows the LCST material 112 to accumulate in thekidney 100 instead of draining out of the ureter 104.

The introduction of other materials in flowable form into the patient'sbody is performed in substantially the same manner as the introductionof LCST material 112 into the patient's body. Materials used inaccordance with the invention include crosslinkable polymers andcrosslinking agents, which catalyze the transformation of thecrosslinkable polymers from a flowable form into a gel form. Theresulting gel is formed of an insoluble network of the crosslinkablepolymers.

Crosslinkable polymers that may be suitable for use in the inventioninclude both ionically crosslinkable and non-ionically crosslinkablepolymers. To be used in conjunction with these crosslinkable polymers,crosslinking agents that may be employed include both ionic crosslinkingagents and non-ionic crosslinking agents, respectfully. Ionicallycrosslinkable polymers include anionic crosslinkable polymers andcationic crosslinkable polymers that may be used in conjunction withanionic crosslinking agents and cationic crosslinking agents,respectively.

The anionic or cationic crosslinkable polymers may include, but are notlimited to, at least one polymer or copolymer such as polyacrylic acids,polymethacrylic acid, alginic acid, pectinic acids, sodium alginate,potasium alginate, carboxy methyl cellulose, hyaluronic acid, heparin,carboxymethyl starch, carboxymethyl dextran, heparin sulfate,chondroitin sulfate, polyethylene amine, polysaccharides, chitosan,carboxymethyl chitosan, cationic starch or salts thereof. Illustrativeexamples of cationic crosslinking agents include polycations such ascalcium, magnesium, barium, strontium, boron, beryllium, aluminium,iron, copper, cobalt, lead, and silver ions. Illustrative examples ofanionic crosslinking agents include polyanions such as phosphate,citrate, borate, succinate, maleate, adipate and oxalate ions, and, morebroadly, anions derived from polybasic organic or inorganic acids. Theanionic or cationic crosslinking agents can either be a mono- orpoly-charged ion.

The crosslinkable polymer also includes non-ionically crosslinkablepolymers that are transformed from a flowable form to a gel form bycontact with non-ionic crosslinking agents. Non-ionic crosslinkingagents may also be used instead of or in addition to ionic crosslinkingagents with ionically crosslinkable polymer. Thus, a higher crosslinkingdensity and improved mechanical properties, i.e., improved stiffness,modulus, yield stress and strength, may be accomplished by additionallysubjecting the ionically crosslinkable polymer to non-ioniccrosslinking. For example, non-ionic crosslinking can be accomplished bytreatment with a chemical crosslinking agent which reacts with groupspresent in the polymer such that covalent bonds are formed connectingdifferent portions of the polymer or between polymer strands to form anetwork.

Suitable non-ionic crosslinking agents are polyfunctional compoundspreferably having at least two functional groups reactive with one ormore functional groups present in the polymer. The crosslinking agentcan contain one or more of carboxyl, hydroxy, epoxy, halogen, aminofunctional groups or hydrogen unsaturated groups. Illustrative non-ioniccrosslinking agents include di-vinylsulfone, polycarboxylic acids oranhydrides, polyamines, epihalohydrins, diepoxides, dialdehydes, diols,carboxylic acid halides, ketenes and like compounds. Illustrativecrosslinkable polymers include those that possess organic acidfunctional groups that are covalently crosslinkable with polyfunctionalcrosslinking agents. The covalent bonds between the crosslinking agentsand the hydrophilic polymers are susceptible to hydrolysis in the body,releasing water-soluble components.

One embodiment utilizes crosslinking agents that can form relativelyweak covalent crosslinking bonds, so that these bonds can bede-crosslinked within the body after a desired length of time. Forexample, polymers comprising covalent bonds that are easily hydrolysableat temperature and pH conditions inside the body can serve this purpose.Such polyfunctional covalent crosslinking agents include polyfunctionalaziridines, polyfunctional carbodiimides, polyisocyanate, glutaraldehydeor other polyfunctional crosslinkers wherein the functional groups arecapable of reacting with the organic acid groups, or any activated formsthereof.

Alginate is an example of an ionically crosslinkable polymer. Alginateis a heterogeneous group of linear binary co-polymer of 1-4 linkedβ-D-mannuronic acid (M) and its C-5 epimer O-L-guluronic acid (G). Themonomers are arranged in blockwise pattern along the polymer chain wheremannuronic blocks (M blocks) and guluronic blocks (G blocks) areinterspaced with sequences containing both M monomers and G monomers(mixed or MG blocks). The proportion and sequential arrangement of theuronic acids in alginate depend upon the species of algae and the kindof algal tissue from which the material is prepared. Commercialalginates are produced from sources including Laminaria hyperborea,Macrocystis pyrifera, Laminaria digitata, Ascophyllum nodosum, Laminariajaponica, Eclonia maxima, Lesonia negrescens and Saragassum sp.

Monovalent cation alginate salts, such as sodium or potassium alginate,are water soluble. Most divalent cations, such as calcium, strontium, orbarium, interact with alginate to form water insoluble but waterpermeable gels. Because of the higher affinity of these divalent cationsfor guluronate compared with mannuronate blocks and because of stericconsiderations, cooperative binding of gelling divalent cations toguluronate within guluronate blocks provides the primary intermolecularcrosslinking responsible for formation of stable alginate gels.Mannuronate and mixed blocks are not crosslinked due to their weakeraffinity for the crosslinking divalent cation, but function as flexibleinterconnecting segments between interacted guluronate blocks.

Different divalent cations have different affinities for mannuronate andguluronate and thus are differentially susceptible to be displaced byexchange with other monovalent or divalent cations. Likewise, dependingon the molecular weight, the number of residues per block and theoverall ratio of guluronate to mixed or mannuronate blocks, differentalginates have different susceptibilities to undergo ion exchangereactions.

The degree of crosslinking, both ionic and non-ionic, can be controlledmainly as a function of the concentrations of the crosslinking agentsand crosslinkable polymers, such as alginate for example. Thecrosslinking agents and crosslinkable polymers may be in a solution ofwater or of another suitable solvent or mixture thereof. The solvent isnot limited as long as it is suitable for the application. In solution,the concentrations of the crosslinking agent or crosslinkable polymerscan range from about 0.0001 M to about 10 M and is to be determinedaccording to the application.

In FIG. 1d, the stone 106 is shown broken apart into fragments, and thisfragmentation can be achieved generally by a medical device thatdelivers light, chemical, physical, or other type of energy to the stone106. Intra-corporeal shock wave lithotripsy (ISWL) is a method offragmenting a stone 106 with vibrational energy produced by a deviceinternal to the patient's body. Energy transferred to stone may emanatefrom a device such as a fragmenting probe 111 placed inside thepatient's body and near the targeted stone 106 in order to fragment thestone 106. The fragmenting probe 111 is inserted into the patient's bodyuntil reaching the general area in which the stone 106 resides. Once thestone 106 is targeted by the fragmenting probe 111, an energy isreleased from the fragmenting probe 111 and is at least partly absorbedby the stone 106 causing the stone 106 to fragment into at least twofragments. The energy released from the fragmenting probe 111 may be inthe form of light from a Holmium laser, vibrational or shockwave energy,for example. The fragmenting probe 111 need not be inserted into thebody via the ureter 104, but may also be inserted percutaneously. Thefragmenting probe 111 may be removed from the patient's body once thefragmentation of the stone 106 is complete. Referring to FIGS. 2a-e, thefragmenting probe 111 is equally effective in the devices and methods inwhich the flowable material is injected into the patient's bodypercutaneously.

In FIG. 1e, a fragment or a whole stone 106 is captured by a medicalretrieval device 114. The retrieval device 114 may be inserted into thekidney 100 via the urinary tract or through the catheter 110 or in someother manner. The retrieval device 114 can be a basket. The basket orother stone capturing device makes contact with the stone 106 andtypically is manipulated by a human operator to ensnare the stone 106.Once the stone 106 is captured, the device 114 can be withdrawn from thebody in order to remove the stone 106. The capture and removal of stones106 or stone fragments can be repeated by reinserting the retrievaldevice 114. The LCST material 112, or other material that forms the gel,functions to stabilize the stones 106 or stone fragments during thepossible multiple rounds of stone removal thus preventing dispersal ofstones 106 or stone fragments throughout the kidney 100.

In FIG. 1f, the retrieval device 114 has been withdrawn from the kidney100. The LCST material 112 in gel form will break down and flush out ofthe body over time. To speed the removal of the gel from the body, achilled fluid can be introduced into the body, but such a proceduregenerally is not required. If used, the fluid could be a physiologicallyacceptable liquid such as water, saline, contrast media, or other fluidhaving temperature below the LCST of the LCST material 112. Thepreferred temperature of the chilled fluid is, for example, −10° C. to20° C., and more preferably 0° C. to 10° C. The fluid may be chilled bypacking the fluid in ice, refrigerating the fluid or other means. Thefluid could be introduced into the gel 112 through the catheter 110. Thecatheter 110 can be used to remove (by, for example, suction) at leastsome of the LCST material 112, whether or not the gel is cooled toreturn it to its flowable liquid form. In one preferred embodiment, acooling fluid is not used in either the delivery or removal of the LCSTmaterial, and instead the gel is eliminated naturally from the body overtime. The catheter 110 could be an independent tubular structure asshown. Alternatively, catheter 110 could be incorporated as part of amedical device that is inserted into the kidney 100 such as a tool thatbreaks apart the stone 106 or collects stone fragments.

The material including crosslinkable polymers that forms a gel may bedissolved to assist in the removal of the gel from the patient's body.The gel formed from crosslinkable polymers may include or be exposed toa de-crosslinking agent which functions by displacing a crosslinkingagent within the network of crosslinkable polymers that forms the gel.Suitable de-crosslinking agents include sodium phosphate, sodiumcitrate, inorganic sulfates, ethylene diamine tetraacetic acid andethylene dime tetraacetate, citrates, organic phosphates (e.g.,cellulose phosphate), inorganic phosphates (e.g., pentasodiumtripolyphosphate, mono- and di-basic potassium phosphate, sodiumpyrophosphate), phosphoric acid, trisodium carboxymethyloxy succinate,nitrilotriacetic acid, maleic acid, oxalate, polyacrylic acid, sodium,potassium, calcium, or magnesium ions.

The de-crosslinking agent may be added to the gel using an appropriatetechnique. Methods for triggered de-crosslinking include administeringor triggering release of the de-crosslinking agent through the diet,administering the de-crosslinking agent directly into the gel in anaqueous solution, encapsulating the de-crosslinking agent in the gel,and enema. Once the de-crosslinking agent comes in contact with the gelformed from crosslinkable polymers, the bonds between the crosslinkablepolymers that create the network that forms the gel will weaken or breakcausing the crosslinkable polymers to transform into a flowable form.Once in a flowable form the crosslinkable polymers can flow out of thepatient's body via the ureter 104 and be extracted by a catheter 110 ora percutaneous access device such as a needle 118.

FIGS. 2a-e generally depict methods and systems of the invention thatare similar to the methods and systems depicted in FIGS. 1a-f. A primarydifference between the two sets of drawings is the way the LCST material112 or other flowable materials that form a gel in the patient's body isintroduced into the patient's body. Referring to FIG. 2a, a needle 118is inserted percutaneously through the skin 116 and into the body of thepatient through the wall of the kidney 100 until reaching the calyx 102.A stone 106 is present in the calyx 102 of the kidney 100. The stone 106could also be located in other locations of the kidney 100 such as therenal pelvis or other locations in the urinary tract such as the ureter104.

LCST material 112, similar to the methods and devices depicted in FIGS.1a-e, is an example of the many types of materials that exist in aflowable form outside the patient's body and are transformed into gelform while in the patient's body. Such materials, that include thecrosslinkable polymers and gelatin materials previously described inFIGS. 1a-e, are equally applicable to the methods and devices describedin FIGS. 2a-e.

The LCST material 112 starts external to the body, at a temperaturebelow body temperature and in a liquid and flowable form. In someembodiments, the LCST material 112 could be cooled to a temperaturebelow ambient air temperature prior to injection to delay the timerequired for the injected LCST material 112 to reach body temperatureand form a gel, but such cooling generally is not required. A mechanism,such as an automated or human-operated syringe, can be used to force theLCST material 112, or other flowable materials, through the needle 118and into the kidney 100, as shown in FIG. 2b. The mechanism can be anysuitable device that applies pressure to the LCST material 112 to forceit in a liquid form through the needle 118 and into the body to contactthe object to be stabilized. The LCST material 112 then enters, as aliquid, areas of the kidney 100 including the calyx 102 and the renalpelvis. The LCST material 112 also generally flows into the ureter 104and towards the urinary bladder, as depicted in FIG. 2b. As thetemperature of the LCST material 112 inside the body rises toward bodytemperature, the LCST material 112 reaches its LCST and transitions intothe gel phase. An object, like the stone 106, in contact with the LCSTmaterial 112 will be at least partially enveloped by the gel and thusstabilized by the gel. The stabilization of the stone 106 allows foreasier capture and retrieval of the stone 106 because the stone 106 isheld in place by the gel 112. Additionally, the transition from liquidto gel can cause the LCST material 112 to form a seal or plug in theureter 104 near the renal pelvis that allows the LCST material 112 toaccumulate in the kidney 100 instead of draining out of the ureter 104.

In FIG. 2c, the stone 106 is shown broken apart into fragments, and thisfragmentation can be achieved by a device that delivers light, chemical,physical, or other type of energy to the stone 106. Following thebreaking apart of the stone 106, the fragments of the stone 106 do notdisperse throughout areas of the kidney. The gel formed from the LCSTmaterial 112 generally does not allow the fragments to escape, and thegel, retains and stabilizes the fragments. The gel generally absorbs atleast some of the energy imparted to the stone 106 to cause it to breakapart, and thus the gel prevents the fragments of stone 106 and thestone 106 itself from dispersing throughout the kidney 100.

Additionally, energy transferred to the stone 106 may emanate fromoutside the patient's body, from a lithotripter 121 for example, andtravel through the patient's body until reaching the stone 106 targetedfor fragmentation in a process called extracorporeal shock wavelithotripsy (ESWL). ESWL is a method of stone fragmentation commonlyused to treat kidney stone disease. Various lithotripters 121 andmethods exist for generating high-intensity, focused shock waves for thefragmentation of objects, such as kidney stones 106, inside a humanbeing and confined in a body liquid. A lithotripter 121 generating aspark gap discharge in water has been used to generate a shock wavewithin an ellipsoidal reflector, which couples and focuses the shockwave to fragment kidney stones 106 inside the patient's body.Lithotripters 121 also exist that use a coil and a mating radiator, inthe form of a spherical segment, to produce magnetically inducedself-converging shock waves that can be directed at a stone 106 withinthe patient's body. A lithotripter 121 also exists that featurespiezoelectric elements arranged in mosaic form on a spheroidal cap havealso been used to produce focused high-intensity shock waves at thegeometric center of the cap, where the stone 106 must be placed.

Following the fragmentation of the stone 106 by ESWL, for example, thefragments of the stone 106 do not disperse throughout areas of thekidney. The gel formed from the LCST material 112 generally does notallow the fragments to escape, and the gel retains and stabilizes thefragments. The gel generally absorbs at least some of the energyimparted to the stone 106 to cause it to break apart, and thus the gelprevents the fragments of stone 106 and the stone 106 itself fromdispersing throughout the kidney 100. ESWL is equally applicable to thesystem and methods described in FIGS. 1a-e.

In FIG. 2d, a fragment or a whole stone 106 is captured by a medicalretrieval device 114. The retrieval device 114 may be inserted into thekidney 100 via the urinary tract or through the catheter 110 or in someother manner. The retrieval device 114 may include a basket. The basketor other stone capturing device makes contact with the stone 106 andtypically is manipulated by a human operator to ensnare the stone 106.Once the stone 106 is captured, the device 114 can be withdrawn from thebody in order to remove the stone 106. The capture and removal of stones106 or stone fragments can be repeated by reinserting the retrievaldevice 114. The LCST material 112 that forms the gel functions tostabilize the stones 106 or stone fragments during the possible multiplerounds of stone removal thus preventing dispersal of stones 106 or stonefragments throughout the kidney 100. Additionally, the needle 118 may beused to extract both the LCST material 112 and the stone fragments 106.

In FIG. 2e, the retrieval device 114 has been withdrawn from the kidney100. The LCST material 112 in gel form will break down and flush out ofthe body over time. To speed the removal of the gel from the body, achilled fluid can be introduced into the body, but such a proceduregenerally is not required. If used, the fluid could be a physiologicallyacceptable liquid such as water, saline, contrast media, or other fluidhaving temperature below the LCST of the LCST material 112. Thepreferred temperature of the chilled fluid is, for example, −10° C. to20° C., and more preferably 0° C. to 10° C. The fluid may be chilled bypacking the fluid in ice, refrigerating the fluid or other means. Thefluid could be introduced into the gel 112 through the needle 118.Additionally, a catheter 110 can be used to remove (by, for example,suction) at least some of the LCST material 112, whether or not the gelis cooled to return it to its flowable liquid form. In one preferredembodiment, a cooling fluid is not used in either the delivery orremoval of the LCST material, and instead the gel is eliminatednaturally from the body over time. The needle 118 could be anindependent tubular structure as shown. Alternatively, needle 118 couldbe incorporated as part of a medical device that is inserted into thekidney 100 such as a tool that breaks apart the stone 106 or collectsstone fragments.

The LCST material 112 used to stabilize an object in the body can alsofunction as a carrier for chemical compounds, drugs, hormones, dyes orother additives to enhance the effectiveness, safety or functionality ofthe gel. The LCST gel mixture may include a dye to aid in determiningthe presence of the LCST material 112. The LCST gel mixture can alsoinclude antibiotics and anti-microbial agents, and such a mixture mayassist in protecting the kidney against infection as a result of aninvasive surgical procedure. The LCST gel mixture can also include oneor more anti-inflammatory agents, which may assist in preventinginflammation in the kidney as a result of an invasive surgicalprocedure. Anesthetic agents may also be included in the LCST mixture inorder to assist in numbing the pain associated with the surgicalprocedure. The LCST material 112 can also contain therapeutic agents.The therapeutic agents may include anti-angiogenic agents such asendostatin, angiostatin and thrombospondin. A LCST mixture containinganti-angiogenic agents could be used to treat cancerous tumors.

The catheter 110 can be used to dispense one or more fluids other thanor in addition to the LCST material. The catheter 110 also can be adilatation catheter with the ability also to dispense one or more fluidsother than or in addition to the LCST material. In one embodiment, thecatheter 110 is 4-8 french in size, and more preferably 5-6 french.

The syringe or other mechanism used to inject the LCST material 112 inliquid form into the body can be, for example, a 5-100 cc syringe suchas a syringe with volume of 5-30 cc or with a volume of 5-10 cc.Pressure applied to the syringe can be applied by hand or by anautomated syringe pusher.

While the invention has been described above mainly in connection withthe stabilization and then removal and/or fragmentation of a kidneystone, the invention has applicability to object stabilization, removal,and fragmentation generally. A variety of stones and other objects,other than kidney stones, can be acted on in accordance with theinvention, such as gall stones and biliary stones. Also, a variety oflocations within the body of a patient can be accessed and treatedaccording to the invention, such as other parts of the male or femaleurinary system, the gastrointestinal system, the biliary system, and thepancreatic duct.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the above-describedstructure and methodology without departing from the scope or spirit ofthe invention.

What is claimed is:
 1. A method for stabilizing an object in a patient'sbody comprising: injecting a first material comprising a crosslinkablepolymer in a flowable form into the patient's body to contact an object;contacting the first material with a second material comprising acrosslinking agent, the first material and second material, uponcontact, forming a gel in the patient's body; and stabilizing the objectin the patient's body by enabling the gel to contact the object.
 2. Themethod of claim 1 wherein the first material comprises one or more of ananionic crosslinkable polymer, a cationic crosslinkable polymer, or anon-ionically crosslinkable polymer.
 3. The method of claim 1 whereinthe first material comprises one or more of polyacrylic acids,polymethacrylic acid, alginic acid, pectinic acids, sodium alginate,potasium alginate, carboxy methyl cellulose, hyaluronic acid, heparin,carboxymethyl starch, carboxymethyl dextran, heparin sulfate,chondroitin sulfate, polyethylene amine, polysaccharides, chitosan,carboxymethyl chitosan, cationic starch or salts thereof.
 4. The methodof claim 1 wherein the second material comprises one or more of ananionic crosslinking ion, a cationic crosslinking ion, or a non-ioniccrosslinking agent.
 5. The method of claim 1 wherein the second materialcomprises one or more of phosphate, citrate, borate, succinate, maleate,adipate, oxalate, calcium, magnesium, barium, strontium, boron,beryllium, aluminium, iron, copper, cobalt, lead, or silver ions.
 6. Themethod of claim 1 wherein the second material comprises one or more ofdi-vinylsulfone, polycarboxylic acids, polycarboxylic anhydrides,polyamines, epihalohydrins, diepoxides, dialdehydes, diols, carboxylicacid halides, ketenes, polyfunctional aziridines, polyfunctionalcarbodiimides, polyisocyanate, glutaraldehyde, or polyfunctionalcrosslinkers including functional groups capable of reacting withorganic acid groups.
 7. The method of claim 1 further comprising thestep of retrieving the object from the gel.
 8. The method of claim 1further comprising the step of applying energy to the object causing itto break into at least two fragments, at least some of the fragmentsremaining at least partially in contact with the gel and stabilized bythe gel.
 9. The method of claim 8 wherein the energy is selected fromthe group consisting of mechanical, vibrational, light, chemical, andelectromagnetic energy.
 10. The method of claim 8 wherein the object isbroken into at least two fragments by technique selected from the groupconsisting of extra-corporeal shock wave lithotripsy, intra-corporealshock wave lithotripsy, or Holmium laser fragmentation.
 11. The methodof claim 8 further comprising the step of retrieving at least some ofthe fragments from the gel.
 12. The method of claim 11 wherein the stepof retrieving at least some of the fragments from the gel includes usinga retrieval device to retrieve such fragments.
 13. The method of claim 1further comprising contacting the gel with a third material comprising ade-crosslinking agent.
 14. The method of claim 13 wherein the thirdmaterial comprises one or more of sodium phosphate, sodium citrate,inorganic sulfates, ethylene diamine tetraacetic acid and ethylene dimetetraacetate, citrates, organic phosphates (e.g., cellulose phosphate),inorganic phosphates (e.g., pentasodium tripolyphosphate, mono- anddi-basic potassium phosphate, sodium pyrophosphate), phosphoric acid,trisodium carboxymethyloxy succinate, nitrilotriacetic acid, maleicacid, oxalate, polyacrylic acid, sodium, potassium, calcium, ormagnesium ions.
 15. A method of fragmenting an object in a patient'sbody comprising: injecting a first material in a flowable form into thepatient's body to contact an object; forming a gel by allowing the firstmaterial to contact a second material in the patient's body; stabilizingthe object in the patient's body by enabling the gel to contact theobject; and applying energy from outside of the patient's body directedtowards the object, the energy breaking the object into at least twofragments.
 16. The method of claim 15 wherein the energy is produced byextra-corporeal shock wave lithotripsy.
 17. The method of claim 15wherein the first material comprises one or more of a crosslinkablepolymer, a gelatin material or a lower critical solution temperaturematerial.
 18. The method of claim 17 further comprising contacting thelower critical solution temperature material with a degradationmodulating material.
 19. The method of claim 18 wherein the degradationmodulating material is selected from the group consisting of pluronicacid, polylactic acid, polyglycolic acid, and hyaluronic acid.
 20. Themethod of claim 15 wherein the first material comprises apolyoxyethylene-polyoxypropylene block copolymer.
 21. The method ofclaim 15 further comprising the step of retrieving the stabilized objectfrom the gel.
 22. The method of claim 15 further comprising the step ofbreaking the object into at least two fragments, at least some of thefragments remaining in contact with the gel.
 23. The method of claim 22further comprising the step of retrieving the at least some of thefragments from the gel.
 24. The method of claim 15 further comprisingdissolving the gel by contacting the gel with a third material thatincludes a de-crosslinking agent.
 25. A system for stabilizing an objectin a patient's body comprising: a first material comprising acrosslinkable polymer in flowable form; a second material comprising acrosslinking agent, such that the first material and second material,upon contact, form a gel in the patient's body; a catheter fortransferring the first material and second material into the patient'sbody in flowable form, such that the gel formed by the first materialand second material contacts and thereby stabilizes the object; and aguide wire for introducing and guiding the catheter into the patient'sbody.
 26. The system of claim 25 wherein the first material comprisesone or more of an anionic crosslinkable polymer, a cationiccrosslinkable polymer, or a non-ionically crosslinkable polymer.
 27. Thesystem of claim 25 wherein the first material comprises one or more ofpolyacrylic acids, polymethacrylic acid, alginic acid, pectinic acids,sodium alginate, potasium alginate, carboxy methyl cellulose, hyaluronicacid, heparin, carboxymethyl starch, carboxymethyl dextran, heparinsulfate, chondroitin sulfate, polyethylene amine, polysaccharides,chitosan, carboxymethyl chitosan, cationic starch or salts thereof. 28.The system of claim 25 wherein the second material comprises one or moreof an anionic crosslinking ion, a cationic crosslinking ion, or anon-ionic crosslinking agent.
 29. The system of claim 25 wherein thesecond material comprises one or more of phosphate, citrate, borate,succinate, maleate, adipate, oxalate, calcium, magnesium, barium,strontium, boron, beryllium, aluminium, iron, copper, cobalt, lead, orsilver ions.
 30. The system of claim 25 wherein the second materialcomprises one or more of di-vinylsulfone, polycarboxylic acids,polycarboxylic anhydrides, polyamines, epihalohydrins, diepoxides,dialdehydes, diols, carboxylic acid halides, ketenes, polyfunctionalaziridines, polyfunctional carbodiimides, polyisocyanate,glutaraldehyde, or polyfunctional crosslinkers including functionalgroups capable of reacting with organic acid groups.
 31. the system ofclaim 25 further comprising a third material comprising ade-crosslinking agent.
 32. A system for stabilizing an object in apatient's body comprising: a first material comprising a crosslinkablepolymer; a second material comprising a crosslinking agent, such thatthe first material and second material, upon contact, form a gel in thepatient's body; and a percutaneous access device for injecting the firstmaterial and second material into the patient's body in flowable form,such that the gel formed by the first material and second materialcontacts and thereby stabilizes the object.
 33. The system of claim 32wherein the first material comprises one or more of an anioniccrosslinkable polymer, a cationic crosslinkable polymer, or anon-ionically crosslinkable polymer.
 34. The system of claim 32 whereinthe first material comprises one or more of polyacrylic acids,polymethacrylic acid, alginic acid, pectinic acids, sodium alginate,potasium alginate, carboxy methyl cellulose, hyaluronic acid, heparin,carboxymethyl starch, carboxymethyl dextran, heparin sulfate,chondroitin sulfate, polyethylene amine, polysaccharides, chitosan,carboxymethyl chitosan, cationic starch or salts thereof.
 35. The systemof claim 32 wherein the second material comprises one or more of ananionic crosslinking ion, a cationic crosslinking ion, or a non-ioniccrosslinking agent.
 36. The system of claim 32 wherein the secondmaterial comprises one or more of phosphate, citrate, borate, succinate,maleate, adipate, oxalate, calcium, magnesium, barium, strontium, boron,beryllium, aluminium, iron, copper, cobalt, lead, or silver ions. 37.The system of claim 32 wherein the second material comprises one or moreof di-vinylsulfone, polycarboxylic acids, polycarboxylic anhydrides,polyamines, epihalohydrins, diepoxides, dialdehydes, diols, carboxylicacid halides, ketenes, polyfunctional aziridines, polyfunctionalcarbodiimides, polyisocyanate, glutaraldehyde, or polyfunctionalcrosslinkers including functional groups capable of reacting withorganic acid groups.
 38. The system of claim 32 further comprising athird material comprising a de-crosslinking agent.
 39. A method forstabilizing an object in a patient's body comprising: injecting a firstmaterial comprising a crosslinkable polymer in a flowable form into thepatient's body to contact an object; contacting the first material witha second material comprising a crosslinking agent, the first materialand second material, upon contact, forming a gel in the patient's body;stabilizing the object in the patient's body by contacting the objectwith the gel; and administering a third material comprising ade-crosslinking agent into the patient's body to dissolve and facilitateremoval of the gel.